Chronic heart failure (CHF) is the only cardiovascular disease in the United States for which the prevalence and morbidity are increasing. Despite treatment advances, 5-year mortality for patients with CHF remains around 50%, with over one million hospital admissions for CHF in 2005. Older women represent 50% of those with CHF in the general population, but limited epidemiologic and treatment data exist in this population because older women account for less than 20% of those enrolled in CHF clinical trials. Hormone replacement therapy (HRT) has a potential role in reducing CHF incidence in women, based on limited data from small, retrospective studies and beneficial effects on endothelial function, neurohormonal activation and myocardial remodeling. However, estrogen-progestin HRT is associated with increased risk of myocardial infarction (MI), an important risk factor for CHF. In addition, there are no data examining HRT in primary prevention of CHF among post-menopausal women, or its effects on survival in women who develop CHF. Given the main results of the Women's Health Initiative (WHI), which showed increased risk for MI, stroke and venous thromboembolic events with HRT, testing our hypothesis in a prospective randomized trial would be difficult. Our objective is to evaluate the association between HRT and risk of incident CHF and subsequent mortality in 27,347post-menopausal women in WHI. The central hypothesis is that HRT will reduce CHF incidence and improve survival among those who develop CHF. Our specific aims include: 1) To investigate the association between HRT and CHF incidence among participants free of CHF at baseline; 2) To examine the association between HRT and all-cause mortality among participants who develop CHF; 3) To explore the association between HRT and CHF incidence and mortality, based on CHF etiology (ischemic versus non- ischemic) and systolic function (impaired versus preserved). The proposed research is innovative because it uses a new approach to identifying CHF cases, using the largest existing database to study the relationship between HRT and CHF in post-menopausal women. The results will further the knowledge on the role of HRT in CHF prevention and/or treatment, and will contribute to the better understanding of CHF epidemiology in older women, who represent a large proportion of the population at risk for CHF. Our study is cost-effective, using data previously collected but never analyzed for this specific purpose. It is unlikely that other cohort studies will be able to provide similar data in the foreseeable future. Chronic heart failure is the only cardiovascular disease in the United States for which the prevalence, morbidity, and mortality are increasing. Despite the fact that women represent up to 50% of the heart failure patients, few epidemiological and clinical studies to date have addressed the gender specific risk factors and treatments for heart failure. Based on limited retrospective data, hormone replacement therapy has a potential role in reducing heart failure incidence and associated mortality in women. Given the main results of the Women's Health Initiative, which showed increased risk for myocardial infarction, stroke and venous thromboembolic events with hormone replacement therapy, testing our hypothesis in a prospective randomized trial would be difficult. The objective of this application is to evaluate the association between hormone replacement therapy and risk of incident heart failure and subsequent mortality in 27,347 post-menopausal women enrolled in Women's Health Initiative. We will be using the largest existing database to study the relationship between hormone replacement therapy and heart failure in post-menopausal women. The results will further the knowledge on the role of hormone replacement therapy in heart failure prevention and/or treatment, and will contribute to the better understanding of heart failure epidemiology in older women, who represent a large proportion of the population at risk for heart failure. [unreadable] [unreadable] [unreadable]